Tofogliflozin attenuates liver steatosis and fibrosis in non-diabetic non-alcoholic steatohepatitis mice

Le résumé fourni par la source

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease with increasing global prevalence. Although diabetes is a major factor in NAFLD progression, up to 75% of the patients with NAFLD do not have diabetes. Tofogliflozin (Tofo), a sodium-glucose cotransporter type-2 inhibitor, is widely used in patients with type 2 diabetes. Several clinical trials with Tofo have shown its beneficial effects in NAFLD patients with diabetes; however, currently, there are limited data on NAFLD patients without diabetes. METHODS: C57Bl/6J mice were fed a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) as a model of non-diabetic non-alcoholic steatohepatitis (NASH). The mice were fed either a normal diet or CDAHFD for 12 weeks, and received either vehicle or Tofo based on their assigned group for 12 weeks. RESULTS: Tofo treatment attenuated CDAHFD-induced liver steatosis and fibrosis. The percentage of monocyte-derived macrophages in the liver, which was significantly increased in the CDAHFD-fed mice, was reduced by Tofo treatment. Furthermore, Tofo treatment increased the hepatic protein and mRNA expression levels related to fatty acid oxidation, which was decreased in CDAHFD-fed mice. Additionally, Tofo treatment decreased the hepatic protein and mRNA expression levels related to fatty acid synthesis, which was increased in CDAHFD-fed mice. CONCLUSION: Tofo may be a potential candidate for inhibiting liver steatosis and fibrosis via an alternative pathway, unlike glucose metabolism, in NAFLD patients without diabetes.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.